Leukotriene Receptor Antagonists/Lipoxygenase Inhibitors

Question 1

MOA for Lipoxygenase Inhibitors

Answer 1

They inhibit the enzyme 5’-lipoxygenase, which is needed to convert arachidonic acid to cysteinyl-leukotrienes (LTC4, LTD4, LTE4) –> decreased plasma exudation, mucus secretion, bronchoconstriction, and eosinophil recrutiment

Question 2

MOA for LT Receptor Antagonists

Answer 2

Inhibit the conversion of Cysteinyl0leukotrienes to Cyst-LT1 receptors –> decreased plasma exudation, mucus secretion, bronchoconstriction, eosinophil recruitment.

Question 3

Zafirlukast & Montelukast

Answer 3

• Selective reversible antagonists of Cysteinyl-leukotriene Rs (CysLT1 Rs)
• PO
• Bronchodilators
• Anti-infalmmatory axn
• Less effective than ICS
• Have glucocoticoids sparing effect (potentiate corticosteroid action)

Question 4

Montelukast

Answer 4

• Primarily prescribed to trx allergies and prevent asthma attacks.
• CI: not indicated for use in reversal of bronchospasm in acute asthma attacks, including status asthmaticus
• Can be continued during acute exacerbations of asthma. Pts who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled beta- agonist.

Question 5

Zafirlukast

Answer 5

• Selective and competitive receptor antagonist of LTD4 & LTE4, components of slow reacting substance of anaphylaxis (SRSA).
• For prophylaxis and chronic trx of asthma in pts 5+.
• HEPATOTOXICITY - cases of life-threatening hepatic failure have been reported in pts who were taking the recommended dose.

Question 6

Zileuton

Answer 6

• Immediate-release tablets were removed from market by controlled-release still available
• Inhibits LTB4, LTC4, LTD4, LTE4 formation
• Used as prophylactic and for chronic trx of asthma in pts 12+
• Not used to trx acute asthma attack
• NOT RECOMMENDED in cases where active liver dz or hepatic function enzymes are 3x+ the upper limit of normal.